Predict gene knockout strategies¶
In cameo we have two ways of predicting gene knockout targets: using evolutionary algorithms (OptGene) or linear programming (OptKnock)
from cameo import models
model = models.bigg.iJO1366
model.solver = "cplex"
wt_solution = model.solve()
growth = wt_solution.fluxes["BIOMASS_Ec_iJO1366_core_53p95M"]
acetate_production = wt_solution.fluxes["EX_succ_e"]
from cameo import phenotypic_phase_plane
p = phenotypic_phase_plane(model, variables=['BIOMASS_Ec_iJO1366_core_53p95M'], objective='EX_succ_e')
p.plot(height=300, points=[(growth, acetate_production)])
OptGene¶
OptGene is an approach to search for gene or reaction knockouts that relies on evolutionary algorithms[1]. The following image from authors summarizes the OptGene workflow.
Every iteration we keep the best 50 individuals so we can generate a library of targets.
from cameo.strain_design.heuristic.evolutionary_based import OptGene
optgene = OptGene(model)
result = optgene.run(target="succ_e",
biomass="BIOMASS_Ec_iJO1366_core_53p95M",
substrate="glc__D_e",
max_evaluations=50000,
robust=False)
Starting optimization at Thu, 14 Jan 2016 15:47:30
Using saved session configuration for http://localhost:5006/
To override, pass 'load_from_config=False' to Session
/Users/joao/.virtualenvs/cameo-py3/lib/python3.4/site-packages/bokeh/session.py:318 [1;31mUserWarning[0m: You need to start the bokeh-server to see this example.
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Finished after 00:50:42
result._processed_solutions
OptKnock¶
OptKnock uses a bi-level mixed integer linear programming approach to identify reaction knockouts[2]:
from cameo.strain_design.deterministic.linear_programming import OptKnock
optknock = OptKnock(model)
Warning: File contains basis. Basis is loaded.
result = optknock.run(max_knockouts=2, target="EX_succ_e", biomass="BIOMASS_Ec_iJO1366_core_53p95M", max_results=2)
---------------------------------------------------------------------------
TypeError Traceback (most recent call last)
<ipython-input-11-277898a50993> in <module>()
----> 1 result = optknock.run(max_knockouts=2, target="EX_succ_e", biomass="BIOMASS_Ec_iJO1366_core_53p95M", max_results=2)
/Users/joao/Documents/repos/cameo/cameo/strain_design/deterministic/linear_programming.py in run(self, max_knockouts, biomass, target, max_results, *args, **kwargs)
234 fluxes_list.append(solution.fluxes)
235 production_list.append(solution.f)
--> 236 biomass_list.append(solution[biomass])
237
238 # Add an integer cut
TypeError: 'LazySolution' object is not subscriptable
result
result.plot(1)
References¶
[1]Patil, K. R., Rocha, I., Förster, J., & Nielsen, J. (2005). Evolutionary programming as a platform for in silico metabolic engineering. BMC Bioinformatics, 6, 308. doi:10.1186/1471-2105-6-308
[2]Burgard, A.P., Pharkya, P., Maranas, C.D. (2003), “OptKnock: A Bilevel Programming Framework for Identifying Gene Knockout Strategies for Microbial Strain Optimization,” Biotechnology and Bioengineering, 84(6), 647-657.